6-35944173-CC-TT

Variant names:

• chr6-35944173-CC-TT
• NM_052961.4:c.2639_2640delGGinsAA
• SLC26A8 p.Arg880Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_052961.4(SLC26A8):​c.2639_2640delGGinsAA​(p.Arg880Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R880W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 0 publications found

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

SLC26A8 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• spermatogenic failure 3

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000304790 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052961.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A8	NM_052961.4	MANE Select	c.2639_2640delGGinsAA	p.Arg880Gln	missense	N/A	NP_443193.1	Q96RN1-1
	SLC26A8	NM_001193476.2		c.2639_2640delGGinsAA	p.Arg880Gln	missense	N/A	NP_001180405.1	Q96RN1-1
	SLC26A8	NM_138718.3		c.2324_2325delGGinsAA	p.Arg775Gln	missense	N/A	NP_619732.2	Q96RN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A8	ENST00000490799.6	TSL:1 MANE Select	c.2639_2640delGGinsAA	p.Arg880Gln	missense	N/A	ENSP00000417638.1	Q96RN1-1
	SLC26A8	ENST00000394602.6	TSL:1	c.2324_2325delGGinsAA	p.Arg775Gln	missense	N/A	ENSP00000378100.2	Q96RN1-2
	SLC26A8	ENST00000355574.6	TSL:2	c.2639_2640delGGinsAA	p.Arg880Gln	missense	N/A	ENSP00000347778.2	Q96RN1-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-35911950;